Our laboratory has shown that oxygen tension is an important regulator of the rate of cell division of cardiac muscule cells in vitro and in vivo. In the present study we hope to clarify the molecular mechanism by which oxygen modifies cell proliferation. Oxygen acts probably to alter the redox state of a control substance (e.g., NAD ion NADH). NAD ion acts as a precursor for poly(ADP-ribose), an inhibitor of DNA which is involved in cell proliferation and cell differentiation. We are studying the participation of poly(ADP-ribose) in oxygen modulated cell proliferation of cardiac myocytes, in oxygen modulated differentiation of skeletal muscle, and in cardiac hypertrophy. We have shown that poly(ADP-ribose) polymerase in cardiac cells has very different kinetic properties (Km, Vmax, and pH optima) when grown in 5% and 20% oxygen. This raises the possible existence of isoenzymes with different functional activity at different oxygen tensions. If the above does indicate the existence of isoenzymes we shall attempt to further characterized their physico-chemical properties in various tissues. We shall also clarify the participation of the poly(ADP-ribose) system in cultures of skeletal muscle,- in the proliferation of myoblasts, in their fusion to form myotubes, and the effects of varying oxygen concentration on the activity of the polymerase enzyme in myoblasts and myotubes.